Table 3.
Main findings from T2D studies investigating genome-wide DNA methylation in human population-based studies.
| Author (year) | Population | Sample size | Gender | Tissue type | Method | Study outcome |
|---|---|---|---|---|---|---|
| Toperoff et al. (79) | Jewish | T2D = 710 Controls = 459 | M and F | WB | Microarray-based methylation assays | Differential methylation identified in 13 CpGs, mapping to SLC30A8, TCF7L2, KCNQ1, FTO, THADA, and JAZF1 genes in T2D subjects compared to controls. |
| Chambers et al. (80) | Indian Asian and European | Indian Asian: T2D = 1,608 Controls = 11 927 European: T2D = 306 Controls = 6,760 | M and F | PB | 450 K | Differential methylation identified in five regions mapping to TCF7L2, FTO, KCNQ1, TXNIP ABCG1, PHOSPHO1, SOCS3, and SREBF1 genes, replicated in two cohorts. |
| Dayeh et al. (81) | European | T2D = 19 Controls = 19 | M and F | WB | 450 K | ABCG1, PHOSPHO1 associated with future T2D risk but not SOCS3, SREBF1 or TXNIP. ABCG1 hypermethylation positively associated with HbA1c and fasting insulin levels. |
| Kriebel et al. (82) | German | 1,448 non-diabetic (FBG and HbA1c) 1,440 non-diabetic (FI and HOMA-IR) 617 non-diabetic (2-h insulin) | M and F | WB | 450 K | DNA methylation at cg06500161 (ABCG1) associated with fasting glucose, fasting insulin, and HOMA-IR. |
| Hidalgo et al. (83) | American | aHealthy individuals = 544 bHealthy individuals = 293 | M and F | WB | 450 K | ABCG1 hypermethylation associated with fasting insulin and HOMA-IR. |
| Walaszczyk et al. (84) | Dutch | T2D = 100 Controls = 100 | M and F | WB | 450 K | Differential methylation of ABCG1, LOXL2, TXNIP, SLC1A5, and SREBF1 associated with T2D. |
| Muftah et al. (19) | aArab, bCaucasian | aT2D = 30 Controls = 93 b180 twins from TwinsUK cohort | M and F | WB | 450 K | Differential methylation identified in TXNIP and DQX1 genes in T2D subjects compared to controls. |
| Kulkarni et al. (85) | Mexican-American | T2D = 174 Controls = 676 | M and F | PB | 450 K | TXNIP, ABCG1, SAMD12 associated with T2D, FBG, and HOMA-IR. |
| Soriano-Tarraga et al. (86) | Caucasian, (Spain) | aT2D = 151 Controls = 204 bT2D = 59 (BISMAR cohort) Controls = 108 bT2D = 63 (REGICOR cohort) Controls = 582 | M and F | WB | 450 K | One differentially methylated region in the TXNIP gene, replicated in 2 independent cohorts. |
| Florath et al. (87) | German | aT2D = 154 Controls = 835 bT2D = 87 Controls = 527 | M and F | WB | 450 K | Differential methylation of TXNIP associated with T2D in discovery and replication cohorts. |
| Jeon et al. (88) | Korean | aHigh-glucose group- 8 T2D = 5 Controls = 13 bT2D = 220 Controls = 220 | M and F | PB | a450 K bBisulfite Pyrosequencing | aMSI2 hypomethylated by 11% in T2D cases and 7% in high glucose cases (p-value = 0.038). CXXC4 hypomethylated by 15% in T2D cases (p-value = 0.044), and 12.8% in high glucose cases (p-value = 0.033).bMSI2 hypomethylation significantly correlated with T2D. |
| Yuan et al. (89) | European | aT2D = 23 Controls = 31 bT2D = 42 Controls = 221 | M and F | WB | aMeDIP-seq and b450 K | Two DMS within a 2 kb region upstream of the transcriptional start site of the MALT1 gene on T2D subjects compared to controls. |
| Matsha et al. (90) | South African, mixed ancestry. | T2D = 3 Prediabetes = 3 Controls = 3 | F | PB | MeDIP-seq | 1,415 DMS in the promoter regions of T2D subjects compared to normoglycaemic controls. Genes associated with cell surface signaling, glucose transport, insulin signaling, pancreas development, and the immune system. |
| Pheiffer et al. (11) | South African, mixed ancestry. | T2D = 3 Prediabetes = 3 Controls = 3 | F | PB | MeDIP-seq | 3,081 DMS in T2D and prediabetic subjects occurred within non-promoter regions, including sites encoding miRNAs. |
a
Discovery cohort;
b
Validation cohort; DMS, differentially methylated sites; F, female; FBG, fasting blood glucose; FI, fasting insulin; HbA1c, glycated hemoglobin A1c; HOMA-IR, homeostatic model assessment-insulin resistance; M, male; MeDIP-seq, Methylated DNA immunoprecipitation sequencing; PB, Peripheral blood; T2D, Type 2 Diabetes; WB, Whole blood; 450 K, Infinium Human-Methylation450 BeadChip.